Childhood Lymphomas classification .pptx

Lymphoma

1. Childhood Lymphomas

2. Objectives: Describe the organ / system of origin. Describe the typical signs and symptoms and common clinical associations. Outline the main features and differences of Non-Hodgkin’s (NHL T and B Cell) and Hodgkin’s Lymphoma. Be aware of the long term complications of tumor treatment as a consequence of chemotherapy, radiotherapy and surgery

3. Childhood Lymphomas Lymphoma is the third most common cancer among children. The two broad categories of lymphoma : Hodgkin disease (HD ): Immune system malignancy, involving B or T lymphocytes. and Non-Hodgkin lymphoma (NHL ): Malignant solid tumor of immune system. Undifferentiated lymphoid cells . Have different clinical manifestations and treatments.

4. HL Histology The pathologic hallmark of HD is the identification of Reed – Sternberg cells in tumor tissue. Reed-Sternberg cells are giant binucleated cells with prominent nucleoli, classically a single giant nucleolus in each nucleus.

5. Histological subtypes 1. Lymphocyte predominance. 2. Mixed cellularity. 3. Nodular sclerosis. 4. Lymphocyte depletion.

6. 1. Nodular sclerosis Hodgkin disease 60-80% of all cases. The morphology shows a nodular pattern. The broad bands of fibrosis divide the node into "nodules." The capsule is thickened. The characteristic cell is the lacunar-type RS cell, which has a monolobulated or multilobulated nucleus and a small nucleolus with abundant and pale cytoplasm. NS frequently is observed in adolescents and young adults and usually involves the mediastinum and other supradiaphragmatic sites.

7. 2. Mixed-cellularity Hodgkin disease 15-30% Histologically , the infiltrate usually is diffuse. RS cells are of the classic type (large, with bilobulate , double or multiple nuclei, and a large eosinophilic inclusion like nucleolus). It commonly affects the abdominal lymph nodes and spleen. Patients with this histology typically have advanced-stage disease with systemic symptoms and immunodeficiency.

8. 3. Lymphocyte-depleted Hodgkin disease Less than 1% The infiltrate in lymphocyte-depleted Hodgkin disease (LDHD) is diffuse and often appears hypocellular . Large numbers of RS cells and bizarre sarcomatous variants are present. It is associated with older age and HIV positivity. Patients usually present with advanced-stage disease. EBV proteins are expressed in many of these tumors. Many cases of LDHD diagnosed in the past actually were non-Hodgkin lymphomas, often of the anaplastic large-cell type.

9. 4. Lymphocyte-rich classic Hodgkin disease 5% . In this type of HD, RS cells of the classic or lacunar type are observed, with a background infiltrate of lymphocytes. It requires immunohistochemical diagnosis. Some cases may have a nodular pattern. Clinically, the presentation and survival patterns are similar to those for MCHD.

10. NHL Histology Pediatric NHLs show diffuse destruction of the lymph node architecture. They are all high-grade malignancies .

11. NHLs categories 1. Small, non-cleaved cell lymphoma : ( Burkitt and non- Burkitt subtypes ). found in about 50% of cases. 2. Lymphoblastic lymphoma : In about 35% of cases. 3. Large cell NHL : In about 15% of cases.

12. Small non-cleaved cell (40-50%) . Mature B-cell phenotype. Burkitt's and non- Burkitt's . 90 % abdomen ( Ascites and intusussception ). Endemic in Africa ( Burkitt's ), with EBV 97%

13. Lymphoblastic (30-35 %). 90 % immature T cells (very similar to T-ALL ). remainder pre-B phenotype (as in ALL ). 50-70% anterior mediastinum,neck , supraclavicular , axillary adenopathy . Classic: older child with intussusception .

14. Large-cell lymphoma (15-20%) Anaplastic (Ki-1) lymphoma – ALK fusion protein. Diffuse Large B-cell lymphoma (DLBCL ). frequent Mediastinal involvement. More like Hodgkin lymphoma than other NHLs. “Peripheral T-cell” lymphoma. Often involves skin, CNS, lymph nodes, lung, testes, muscles, and GI tract .

15. Clinical Presentation The most common first clinical manifestation of HL or NHL is painless lymph node enlargement . Most often in the cervical & supraclavicular chains. The onset is typically sub acute and prolonged for HL and rapid through the course of a few days or weeks for NHL.

16. Clinical Presentation\HL Patients commonly present with painless, non-tender, firm, rubbery, cervical or supraclavicular lymphadenopathy . Patients may present signs of airway obstruction ( dyspnea , hypoxia, cough), pleural or pericardial effusion (Rarely, hemoptysis is observed). Hepatocellular dysfunction, or bone marrow infiltration . Patients may present with pruritus .

17. Clinical Presentation Splenomegaly or\and hepatomegaly may be present. Asymptomatic discovered by CXR. Systemic symptoms, classified as B symptoms (present in 40% of patients) are: Unexplained fever > 39°C. Weight loss >10% total body weight over 6 mo. Drenching night sweats.

18. Etiology\ HL The etiology of HD is unknown. Epstein-Barr virus (EBV). HIV infection. Genetic : Approximately 1% of patients with HD have a family history of the disease. Siblings of an affected individual have a 3- to 7-fold increased risk for developing HD. This risk is higher in monozygotic twins. (HLA-DP alleles are more common in HD ).

19. Clinical Presentation\NHL Depend primarily on pathological subtype and sites of involvement . Constitutional symptoms are uncommon, except in patients with anaplastic LCL, many of whom exhibit low-grade fever, malaise, anorexia, or weight loss. 70 % present with advanced stages III or IV including extra nodal disease as: GIT: abdominal pain, constipation, mass, or ascites . Bone marrow ( generalized or migratory bone pain, significant cytopenias are uncommon ) . And

20. Clinical Presentation Central nervous system (CNS) involvement : Uncommon at diagnosis . But : Headache, meningismus , cranial nerve palsies, and altered sensorium may be observed. Patients with NHL (particularly SNCCL) occasionally present with symptoms suggestive of meningoencephalitis .

21. Clinical Presentation Localized disease can present as: lymphadenopathy (usually firm and nontender ). Tonsillar hypertrophy. Or A mass in virtually any location. However , NHL is primarily an extranodal disease in children . BL commonly presents with abdominal or head and neck disease with involvement of the bone marrow or CNS. LL commonly presents with an intrathoracic or mediastinal supradiaphragmatic mass, and may spread to the bone marrow and CNS.

22. Clinical Presentation In general, patients often appear mildly to moderately ill and occasionally have a low-grade fever. They may present with pallor, respiratory distress, pain, and discomfort. A jaw or orbital mass may be present in as many as 10% of patients in developed countries and is very common in African patients with endemic BL. A cervical or supraclavicular mass or adenopathy is firm, fixed, and nontender .

23. Clinical Presentation Dyspnea or stridor may be present with a mediastinal mass . With superior vena cava syndrome, distended neck veins and plethora also may be observed. Decreased breath sounds are heard secondary to bronchial obstruction or pleural effusion. Thoracic dullness to percussion may be present with pleural effusion.

24. Clinical Presentation Abdominal distension or mass may be present with or without tenderness, rebound tenderness, and/or shifting dullness. Painful skin lesions are suggestive of anaplastic LCL. Less common physical findings include: Nasopharyngeal mass. Parotid enlargement. Nephromegaly , and Testicular enlargement . Focal extremity pain or swelling may be present with primary bone lymphoma . Obtundation , agitation, and meningismus may be observed in individuals with CNS involvement.

25. Etiology\ NHL In developed countries, most individuals with NHL have no known etiology or association . Immunosuppression and viral infection Immunosuppressed individuals ( eg , HIV positive, post–bone marrow transplant) are at higher risk of developing NHL, particularly SNCCL and LCL of B-cell origin. Epstein-Barr virus, which causes B-cell proliferation has been implicated in most of these lymphomas. Primary CNS lymphoma is more common in these patients . Patients successfully treated for Hodgkin disease are at increased risk of developing NHL

26. Etiology\ NHL Location In sub-Saharan Africa, a strong association exists between the development of endemic BL and prior exposure to both malaria (with resultant T-cell suppression) and Epstein-Barr virus. In addition, exposure to 4-deoxyphorbol ester from the plant Euphorbia tirucalli (via goat's milk) tentatively has been implicated in the pathogenesis of endemic BL.

27. Etiology\ NHL Genetic: 80% of BL patients has t(8;14)(q24;q32) translocation . Most anaplastic (T-lineage) LCLs in children exhibit a t(2;5)(p23;q35) translocation.

28. Diagnosis Any patient with persistent, unexplained lymphadenopathy unassociated with an obvious underlying inflammatory or infectious process should have a chest radiograph to identify the presence of a mediastinal mass before node biopsy

29. Diagnosis Lymph node or tissue biopsy is mandatory for histological diagnosis. Excisional biopsy is preferred over needle biopsy to: Ensure that adequate tissue is obtained, for appropriate: Immunocytochemical and molecular studies. Culture and Cytogenetic analysis

30. Recommended Diagnostic Evaluation for Children Who Have Lymphoma 1. Complete history and physical examination. 2. Complete blood count with differential count, erythrocyte sedimentation rate. 3. Chemistries: Renal (Rarely, HD is associated with nephrotic syndrome ) and hepatic function tests. Serum electrolytes, and mineral panel.

31. Diagnostic Evaluation 4. Serum lactate dehydrogenase (may correlate with the bulk of disease ), uric acid and alkaline phosphatase . 5. Imaging studies: Chest radiograph. Computed tomography (CT) of neck and chest. CT or magnetic resonance imaging of abdomen and pelvis. Gallium scan. Bone scan. 6. Bone marrow examination. 7. Cerebrospinal fluid examination ( cytology).

32. Chest CT scan PET scans

33. Massive mediastinal T-lymphoblastic lymphoma Non-Hodgkin lymphoma of the terminal ileum Malignant pleural effusion. Massive left pleural effusion

34. Lymphoma Staging Murphy  Ann Arbor I: tumor at one site (nodal or extranodal -- “E”) II: two or more sites; same side of body (or resectable GI primary) III: both sides of body but not IV (& unresec . GI & mediastinal for NHL) IV: CNS or marrow involvement (Murphy); lung, liver, marrow, or bone for Ann Arbor

35. Prognosis FAVORABLE: <10 years. Female. favorable subtypes (LP and NS) and Stage I non-bulky disease. UNFAVORABLE: Persistently elevated ESR. LD histopathology. bulky disease--largest dimension > 10cm. B symptoms.

36. Treatment Options of lymphomas: Supportive – Tumour lysis . – Neutropenic sepsis. – Nutrition. – Organ dysfunction.

37. Treatment Chemotherapy With overall cure rates 60-80 +%. High risk of tumor lysis and hyperuricemia . – Multi-agent: ( cyclophosphamide , doxorubicin, vincristine , prednisone [CHOP]) – Intensive Radiotherapy in special cases. Second malignancy risks. Sterility risks.

38. Thank you